Chemical synthesis of ethyl picolinate (2) (Abbas et al. 2015)

Chemical synthesis of picolinohydrazide (3) (Abbas et al. 2015)

General method for synthesis of the target compounds (4–7) (Najeh Al-Saad et al. 2019)

Synthesis of N-(4-nitrophenyl)-2-picolinoylhydrazinecarbothioamide (4)

Synthesis of N-(4-bromophenyl)-2-picolinoylhydrazine- carbothioamide (5)

Synthesis of N-(4-fluorophenyl)-2-picolinoylhydrazinecarbothioamide (6)

Synthesis of 2-picolinoyl-N-(p-tolyl)hydrazinecarbothioamide (7)

Chemical synthesis of the target compounds (5A, 6A, and 7A) (Amir et al. 2007; Choi et al. 2019)

Synthesis of 4-(4-bromophenyl)-5-(pyridin-2-yl)-4H-1,2,4-triazole-3-thiol (5A)

Synthesis of 4-(4-fluorophenyl)-5-(pyridin-2-yl)-4H-1,2,4-triazole-3-thiol (6A)

Synthesis of 5-(pyridin-2-yl)-4-(p-tolyl)-4H-1,2,4-triazole-3-thiol (7A)

Chemical synthesis of the target compounds (5B, 6B, and 7B) (Amir et al. 2007; Choi et al. 2019)

Synthesis of N-(4-bromophenyl)-5-(pyridin-2-yl)-1,3,4-thiadiazol-2-amine (5B)

Synthesis of N-(4-fluorophenyl)-5-(pyridin-2-yl)-1,3,4-thiadiazol-2-amine (6B)

Synthesis of 5-(pyridin-2-yl)-N-(p-tolyl)-1,3,4-thiadiazol-2-amine (7B)

Chemical synthesis of the target compounds (5C, 6C, and 7C) (Amir et al. 2007; Choi et al. 2019)

Synthesis of N-(4-bromophenyl)-5-(pyridin-2-yl)-1,3,4-oxadiazol-2-amine (5C)

Synthesis of N-(4-fluorophenyl)-5-(pyridin-2-yl)-1,3,4-oxadiazol-2-amine (6C)

Synthesis of 5-(pyridin-2-yl)-N-(p-tolyl)-1,3,4-oxadiazol-2-amine (7C)

Cell culture

In vitro cytotoxicity MTT assay

Detection of apoptosis

Quantitative reverse transcription polymerase chain reaction (qRT-PCR)

Western blot analysis

Cytochrome c release apoptosis assay

Statistical analysis

Molecular docking study

Compound 5 causes cytotoxicity in human A549 lung cancer cells

Compound 5 cytotoxicity is cancer-cell specific

Cytotoxicity of compound 5 is attributed to induction of apoptosis

Compound 5 induction of apoptosis is dependent on activation of caspase 3, 4, and 9

Compound 5 induces apoptosis through the ER stress pathway

Compound 5 inhibits EGFR when analyzed by molecular docking but not when studied in vitro